N-cadherin attenuates nucleus pulposus cell senescence under high-magnitude compression

Abstract

Mechanical compression is important in disc degeneration. N-cadherin (N-CDH)-mediated signaling contributes to the maintenance of the normal nucleus pulposus (NP) cell phenotype and NP matrix biosynthesis. Our preliminary study demonstrated that a high-magnitude compression (20% deformation) promotes NP cell senescence in a three-dimensional scaffold culture system. The aim of the present study was to investigate whether N-CDH-mediated signaling alleviates NP cell senescence under the above-mentioned high-magnitude compression. NP cells were transfected with recombinant lentiviral vectors to enhance N-CDH expression. All the transfected or un-transfected NP cells were seeded into the scaffolds and subjected to 20% deformation at a frequency of 1.0 Hz for 4 h once per day for 5 days. Results indicated that N-CDH overexpressed NP cells exhibited decreased senescence-associated β-galactosidase activity and downregulated expression levels of senescence-associated markers (p16 and p53). Furthermore, the N-CDH overexpressed NP cells exhibited increased cell proliferation potency, telomerase activity and matrix biosynthesis compared with NP cells without N-CDH overexpression under high-magnitude compression. Thus, N-CDH-mediated signaling contributes to the attenuation of NP cell senescence under high-magnitude compression.